The Mechanism Of Interaction Between TREM-1 And TLR4 In The Formation Of Early Brain Injury After Subarachnoid Hemorrhage

Objective:To explore the effect and potential mechanisms of TREM-1 in early brain injury after SAH and the potential TLR4/My D88/NF-κB pathway.Methods:First,the endovascular perforation SAH model was produced.The TREM-1 agonist TREM-1m Ab and the antagonist LP17 were selected to intervene in rats.120 SD rats were randomly divided into: sham operation group(Sham group),SAH+normal saline group(Vehicle group),SAH+TREM-1m Ab group(Agonist group)and SAH+LP17 group(Antagonist group),with 30 rats in each group.Rat brain tissues were taken at 24 h and 72 h after operation to analyze the degree of brain edema and BBB destruction at 24 h and 72 h,as well as the protein expression of TREM-1,TLR4,My D88 and NF-κB at 24 h.Second,use the same method to produce SAH model.TAK-242,an inhibitor of TLR4,was used to intervene in rats.72 SD rats were randomly divided into: Sham group,SAH group,Sham+TAK-242 group and SAH+TAK-242 group,with 18 rats in each group.The brain tissues of the rats were taken 72 hours after the operation to analyze the degree of brain edema and BBB destruction,as well as the protein expression of TLR4 and TREM-1.Finally,the cerebrospinal fluid of 34 SAH patients was collected clinically,and the concentration of s TREM-1 in the cerebrospinal fluid was measured by enzyme-linked immunosorbent assay(ELISA),and the relationship between s TREM-1 and Hunt-Hess scale score was analyzed.Results:1.Overexpression of TREM-1 reduces the neurological function score,and aggravates the degree of EBI by destroying BBB permeability and brain edema,while inhibiting TREM-1 and TLR4 reduces the degree of EBI,and the difference of neurological function score,BBB damage and brain edema was statistically significant(P<0.05).2.TREM-1 overexpression increases the expression of TLR4,My D88 and NF-κB,while inhibiting the expression of TREM-1 decreases the expression.At the same time,inhibiting TLR4 also reduces the expression of TREM-1,and the difference in protein expression levels is statistically significant.(P<0.05).3.ELISA analysis showed that there was a significant correlation between the concentration of s TREM-1 in the cerebrospinal fluid of SAH patients and the Hunt-Hess scale score(r=0.769,P<0.001),and among the Hunt-Hess grade I-II,III,IV-V,there was a statistically significant difference in the concentration of sTREM-1(P<0.05).Conclusion:1.TREM-1 can mediate the formation of EBI after SAH by regulating the TLR4/My D88/NF-κB pathway,and TLR4 can in turn regulate the expression of TREM-1.2.s TREM-1 in the cerebrospinal fluid of SAH patients is expected to be a biological marker for assessing the severity of the disease.